Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF-mediated endothelial migration, capillary tube formation and neo-vascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.
Funding
Thrombin Induced Pulmonary Vascular Permeability | Funder: National Institutes of Health (National Heart, Lung, and Blood Institute) | Grant ID: R01HL045638
Training Program In Lung Biology And Pathobiology | Funder: National Institutes of Health (National Heart, Lung, and Blood Institute) | Grant ID: T32HL007829
Regulation of Wnt Sinaling by PAP During Angiogenesis | Funder: National Institutes of Health (National Heart, Lung, and Blood Institute) | Grant ID: R01HL079356
Role of End Binding 3 in Mechanism of vascular permeability | Funder: National Institutes of Health (National Heart, Lung, and Blood Institute) | Grant ID: R01HL103922
Role of Vascular Endothelial Growth Factor Receptor 2 Trafficking by Kinesin in Angiogenesis | Funder: Addgene | Grant ID: 13SDG14680053
History
Citation
Yamada, K. H., Nakajima, Y., Geyer, M., Wary, K. K., Ushio-Fukai, M., Komarova, Y.Malik, A. B. (2014). KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2. Journal of Cell Science, 127(20), 4518-4530. https://doi.org/10.1242/jcs.156109